Aldehydes Aniline

As in the case of Diels-Alder reactions, aqueous aza-Diels-Alder reactions are also catalyzed by various Lewis acids such as lanthanide triflates.113 Lanthanide triflate-catalyzed imino Diels-Alder reactions of imines with dienes or alkenes were developed. Three-component aza-Diels-Alder reactions, starting from aldehyde, aniline, and Danishefsky s diene, took place smoothly under the influence of HBL4 in aqueous media to afford dihydro-4-pyridone derivatives in high yields (Eq. 12.46).114... 

The commercially important representatives of group 4 are diphenyl guanidine and diortho tolyl guanidine. Group 5 includes a number of aldehyde aniline reaction products such as formaldehyde aniline, ethyledene aniline, butraldehyde aniline, heptaldehyde aniline hexa methylenetetraamine and acet-aldehydeaniline. Aetaldehyde, butraldehyde and heptaldehyde derivatives of aromatic amines are powerful accelerators. 

Microwave irradiation considerably improved the reaction speed and yields of 2,4-disubstituted quinolines in a MCR of aldehydes, anilines and alkynes [111]. The cyclocondensation was catalyzed by montmorillonite clay doped with copper bromide and was completed within 3-5 minutes (pulsed irradiation technique—1 min with 20 s off interval), when performed in a household microwave oven. Oil-bath heating at 80 °C for 3-6 hours was necessary to achieve comparable yields of quinolines (71-90%) (Scheme 42). 

Based on this and earlier work, Kobayashi et al. in 1998 reported initial investigations of three-component reactions of aldehydes, anilines and allyltributylstannane to give homoallylic amines 4 [6]. With the catalyst Sc(OT03 in the presence of sodium dodecyl sulfate for building a micellar system, yields in the range 66- 90 % were obtained (Scheme 1). The stability of the catalyst towards oxygen is noteworthy. 

Anhydro farm aldehyde aniline Trimeric Methyl-eneaniline or 1,3,5-Triphenyl-trimethylenetri-amine, H C------N(C,H, )--< H,... 

A solid-phase Ugi-Reissert reaction on chloroformate resin, has been reported. The product, the ot-carbamoylated isoquinoline 230, is released by oxidative cleavage (Scheme 33a). Interestingly, the enamide moiety in the adduct can be exploited to perform this process in tandem with a Povarov MCR [189, 190]. In this way, by interaction of dihydroisoquinoline 231 with aldehydes, anilines and a suitable Lewis acid catalyst, the polyheterocyclic system 232 was prepared (Scheme 33b). The Zhu group devised an innovative approach for the synthesis of this class of compounds. They employed the heterocyclic amine 233, which was oxidized in situ to the dihydroisoquinoline 234 with IBX, to undergo the classic Ugi reaction. Remarkably, all the components are chemically compatible, allowing the sequence to proceed as a true MCR (Scheme 33c) [191]. 

Selective reduction of a halogenated aromatic nitro compound to the corresponding hydroxylamine or amine upon irradiation of Ti02 suspended in degassed alcohol has also been reported, as has the selective photoreduction of / -nitrobenzaldehyde to the corresponding aldehydic aniline (Eq. 30) [170], and alkyl azides can also be reduced to the corresponding amine. 

Akiyama et al. have reported that the cycloaddition of 102 to imines is effectively accelerated by 10 mol% of a Bronsted acid such as HBF4 in aqueous media, affording dihydro-4-pyridones in good to high yield (Scheme 10.109) [295]. This catalytic system is applicable to three-component synfhesis of dihydro-4-pyridones from aldehydes, anilines, and 102. The three-component coupling can be achieved efficiently in water without any organic solvent by using SDS as surfactant. 

Sc(OTf)3 and Yb(( ) l r), are quite valuable catalysts of the aza-DA reaction of 102 [204] (Scheme 10.113). Wifh these catalysts, three-component coupling of aldehydes, anilines, and 102 proceeds smoothly [304]. Sc(OSO2C8Fi7)3 enables an efficient aza-DA reaction in supercritical CO2 [305]. Cationic lanthanide complexes, [(C5Me5)2Ce][BPh4] and fhe corresponding Sm and La complexes, have high catalytic activity in the HDA reaction of 102 with aromatic aldehydes [306]. 

The three component condensation employing aldehydes, anilines and electron-rich olefins leading to substituted tetrahydroquinolines 93 constitutes an attractive approach for combinatorial and parallel synthesis (Scheme 3.6.13). 

Non-chloroaluminate ILs, which are in general poor nucleophiles, have proven to be attractive alternative media for Lewis acid catalyzed reactions. ILs may have a reaction rate accelerating effect, and they may improve selectivity and facilitate catalyst recovery. This is the case for scandium triflate catalyzed Diels-Alder cycloaddition [8,9], three-component (aldehyde, aniline, triethylphosphite) synthesis of a-aminophosphonates [10], Claisen rearrangement and cyclization reactions [11], or Friedel-Crafts reactions [12, 13]. 

The reaction of aldehydes, anilines and enecarbamates in dichlo-romethane in the presence of EtOH and a catalytic amount of the chiral phosphoric acid (225) afforded Mannich adducts which were in situ reduced to a ti-l,2-disubstituted 1,3-diamines (224) in excellent diastereoselectivity and enantioselectivity (Scheme 62). " ... 

Several series of complexes substituted in the aldehyde, aniline, or both rings by alkanoyloxy chains have also been prepared and investigated. Sirigu showed that the copper complexes ((212) M = Cu R, R = C H2 +iC02, m = 5-11) had SmC phases (and an additional SmA phase for one compound with ra=6) typically in the range 180 210 °C the palladium derivative of the... 

Tu et al. have reported the synthesis of 4-aza-podoplyllotoxin via a three-component reaction of an aldehyde, aniline and cyclic diones in H2O under MWl. Use of tetronic acid as the cyclic diketone provided the 4-aza-podophyllotoxin derivatives (76) (Scheme 6.30). The reaction proceeded via the attack of Schiff s base, formed through the condensation between aldehyde and aniline, on tetronic acid resulting into an intermediate which underwent intramolecular cyclization and dehydration to yield the product. The scope of the strategy was enhanced by replacing tetronic acid with 1,3-indanedione to generate indenoquinoline derivatives (77) [69]. 

Verbindung C 5H]7C1N202( ) aua Indol aldehyd-anilin 21 II262. 

Catalyst 3-(iV7V-dimethyldodecylammonium)propanesulfonic acid ([DDPA][HS04]) Keywords Aromatic aldehydes, anilines, triethylphosphite/diethylphosphite, [DDPA][HS04] (IL), room temperature, One-pot multi-compruient reaction, a-aminophosphonates... 

To avoid the use of organic solvents in Diels-Alder reactions, ionic liquid was recognized as a promising alternative solvent because its specific features of excellent solubility, lack of volatility, tunable polarity, and stable reusability [27]. 8-Ethyl-1,8-diazabicyclo[5,4,0]-7-undecenium trifiuoromethanesulfonate ([Et-DBUjOTf) was utilized as a recoverable medium for Sc(OTf)3-catalyzed one-pot aza-Diels-Alder reactions of aromatic aldehydes, anilines and Danishefsky s diene (Scheme 12.15) [28]. In this reaction system, Sc(OTf)3 is recovered smoothly in... 

Considering the water tolerance of lanthanide Lewis acids, a logical extension of the above-mentioned three-component coupling reaction is the reaction in aqueous media. Kobayashi et al. reported Mannich-type reaction of aldehydes, aniline derivative, and methyl enol ethers with 10mol% of Yb(OTf)3 in THF/H2O solvent system (Table 13.4) [8]. Applicability of commercially available aqueous formaldehyde and chloroacetaldehyde solution is of particular importance from the synthetic point of view (entries 1-3). A wide variety of aldehydes were transformed... 

Chiral Brpnsted acids have also been shown to effectively catalyze the Mannich reaction between aldehydes, anilines, and enecarbamates [100]. Here, the application of enecarba-mates as nucleophilic species instead of ketones gives access to enantioenriched 1,3-diamines after subsequent reduction in situ with sodium cyanoborohydride. The potential of this approach was demonstrated by reacting various aromatic or aliphatic aldehydes and substituted enecarbamates with para-nitroaniline in the presence of the chiral phosphoric acid catalyst 150 (Scheme 11.34). 

Synthetically important chiral 1-monosubstituted 1,3-diamines (145) are synthesized in Mannich-t)fpe reactions of enecarbamates (140) with aromatic and aliphatic hemiaminal ethers (141) in the presence of phosphoric acid 95a. This process involves the highly reactive Mannich-t)fpe product (144), which is entrapped by a methanol molecule generated during the formation of the imine (143) derived from the hemiaminal ether (141) (Scheme 28.15) [72]. Similarly, diastereo- and enantio-enriched anti-l,2-disubstituted 1,3-diamines are prepared by the Mannich-type reaction of aldehydes, anilines, and enecarbamates in the presence of chiral phosphoric acid [73]. 

Highly enantioselective, three-component, inverse electron-demand aza-Diels-Alder reaction of aldehydes, anilines, and isoeugenol derivatives (129) catalysed by a phosphoric acid (119) has been reported by Masson and co-workers. A wide variety of 2,3,4-trisubstituted tetra-hydroquinolines (130) containing an aryl group at the 4-position were obtained in a one-pot process with good to high yields and excellent enantioselectivities (up to >99% ee) (Scheme 45). ... 

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